{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:30:20Z","timestamp":1790847020030,"version":"4.1.0"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\nObjective To elucidate the molecular mechanism which causes thyroid dysgenesis (TD) in a boy with brain-lung-thyroid syndrome.<\/jats:p><jats:p>\nDesign, patients, measurements We describe a patient with TD, respiratory disease and cerebral palsy who is heterozygous for mutations in two different genes, the PAX8 (p.E234K) and the NKX2.1 (p.A329GfsX108). In vitro studies were performed to functionally characterize these mutations. Congenital hypothyroidism (CH) was identified by neonatal screening associated with a hypoplastic thyroid gland. Postpartum he developed a brain-lung-thyroid syndrome with severe respiratory failure, symptomatic epilepsy and a considerable psychomotor retardation. The DNA-binding capability and the transcriptional activity of the two mutated transcription factors were investigated in vitro.<\/jats:p><jats:p>\nResults The NKX2.1 mutation did not show any transcriptional activity and had almost no DNA-binding. The PAX8 mutation was normally located to the nucleus and showed a normal transactivation and a normal binding to the known downstream targets.<\/jats:p><jats:p>\nConclusions The molecular defect explaining the phenotype of brain-lung-thyroid syndrome was identified. To what extent the PAX8 mutation contributes to the phenotype needs to be further investigated. We recommend to screen patients with CH and TD for mutations in all known TD candidate genes.<\/jats:p>","DOI":"10.1055\/s-0043-119875","type":"journal-article","created":{"date-parts":[[2017,9,27]],"date-time":"2017-09-27T23:22:26Z","timestamp":1506554546000},"page":"85-90","source":"Crossref","is-referenced-by-count":11,"title":["Novel Mutations in the NKX2.1 gene and the PAX8 gene in a Boy with Brain-Lung-Thyroid Syndrome"],"prefix":"10.1055","volume":"126","author":[{"given":"Pia","family":"Hermanns","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Johannes Gutenberg University Medical School, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Kumorowicz-Czoch","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Endocrinology, Chair of Pediatrics, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow, Poland"},{"name":"Private Pediatrics and Pediatric Endocrinology Practise, Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Grasberger","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Refetoff","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Departments of Medicine and Pediatrics, The University of Chicago, Chicago, IL, USA"},{"name":"Departments of Medicine and Genetics, The University of Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Pohlenz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Johannes Gutenberg University Medical School, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2017,9,27]]},"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-119875.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,2,19]],"date-time":"2018-02-19T23:31:00Z","timestamp":1519083060000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-119875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,27]]},"references-count":0,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2018,2,19]]},"published-print":{"date-parts":[[2018,2]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-119875","relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,27]]}}}